Plasma levels of high-density lipoproteins (HDL) and apolipoprotein AI (ApoAI) are inversely associated with cardiovascular morbidity and mortality. ApoAI is primarily synthesized in the liver and small intestine, and comprises a single polypeptide of 243 amino acid residues with a molecular weight of approximately 28,000 Da. ApoAI, through activation of lecithin:cholesterol acyltransferase, catalyzes the reaction of cholesterol and phosphatidylcholine to yield cholesterol esterified with a long-chain fatty acid and 2-lysophosphatidylcholine, an important step in reverse cholesterol transport.
The importance of HDL cholesterol as an independent risk factor for coronary artery disease (CAD) is well known. Novel therapeutic approaches for administering HDL protein, ApoAI, or ApoAI analogues to alter the development of atherosclerosis have been investigated in animal models and in humans. In fact, individuals with ApoAI deficiency and ApoAI-deficient mice fail to form normal HDL particles and, as a result, are predisposed to premature CAD.
Recent studies have also shown anti-inflammatory properties of ApoAI. For example, the inhibitory activity of ApoAI appears to be specifically directed to contact-mediated monocyte activation by T-cells through inhibition of TNF-α and IL1β. In addition to anti-inflammatory and anti-atherogenic function, reduced plasma concentrations of HDL and ApoAI have been implicated in the development of Type 2 diabetes.